This project is designed to evaluate the potential developmental toxicity of perturbations in embryonic energy producing pathways using the whole embryo culture technique. The whole embryo culture system supports the normal growth and development of rodent embryos in an in vitro system and allows for the evaluation of the effects of an agent on the developmental processes. A number of metabolic inhibitors (2-deoxyglucose, 3- chlorolactaldehyde, dichloroacetate, fluoroacetate, iodoacetate, rhodamine 123, dinitrophenol, dicyclohexylcarbonyldiimide, and cyanide) will be used in order to produce specific metabolic perturbations in the conceptus during the critical period of organogenesis. The relationship between specific metabolic perturbations and energy production and homeostasis will be determined. Additionally, the relationships between the biochemical effects and the resulting morphological effects of these treatments will be evaluated. Another aspect of this project will be to evaluate the mechanisms associated with biochemical maturation that occurs in the conceptus during the period of organogenesis. This project will involve an analysis of metabolic changes throughout organogenesis and the enzymatic sequelae related to the changing metabolism during development.